Studies have been proposed on the continued isolation and identification of the purative GH-releasing hormone (GH-RH), PRL-inhibiting factor (PIF), and PRL-releasing hormone (PRH) from porcine hypothalami using purification schemes already established for isolation of "GH-RH" and "PIF" and established in vitro and in vivo systems to measure these activities. Although some evidence has been obtained for the existence of PRH during our studies on the purification of hypophysiotropic hormones, it has been minor; nevertheless, an attempt will be made to isolate and identify this hormone mainly on the basis of evidence of other investigators that it does exist. Also, we will continue to synthesize TRH analogs with greater agonist/antagonist activity. The other aspect of our studies involves an empirical-theoretical-biological approach for the purpose of learning more about the structure-activity relationships of small synthetic peptides that have hypophysiotropic activity. A special effort will be made to understand the possible chemical structural interrelationships of the EK-like peptides which stimulate GH release and the somatostatin (SS) analogs which inhibit GH release. We feel this type of experimental data will reveal the values and limitations of the theoretical approach being used for discovering new peptides with hypophysiotropic activity. The low energy conformations of small peptides by computer analysis could facilitate the understanding of peptide structure-activity relationships and aid in designing new peptides that are not only more potent but also that act more specifically on the pituitary, pancreas, and brain.